TMEM164 promotes ferroptosis by selectively mediating ATG5-dependent autophagosome formation to inhibit the

Yongxiang Su1, Lintao Li2, Junhai Chen2

  • 1Department of Surgical oncology, Fudan University Shanghai Cancer Center Xiamen Hospital (Xiamen Cancer Hospital), Xiamen City, China.

Autoimmunity
|October 11, 2024
PubMed

Insights

Transmembrane protein 164 (TMEM164) is downregulated in lung adenocarcinoma (LUAD), hindering anti-tumor immunity. Restoring TMEM164 promotes ferroptosis and enhances anti-cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Lung adenocarcinoma (LUAD) has a low five-year survival rate despite treatment advances.
  • Targeting novel pathways is crucial for improving LUAD patient outcomes.

Purpose of the Study:

  • Investigate the role of transmembrane protein 164 (TMEM164) in LUAD.
  • Explore TMEM164's involvement in ferroptosis and anti-tumor immunity.
  • Evaluate TMEM164 as a potential therapeutic target for LUAD.

Main Methods:

  • Utilized cell-based assays (QPCR, WB, CCK-8, EdU, Transwell, flow cytometry, CO-IP).
  • Employed animal models with histological analysis (HE staining, IHC).
  • Examined TMEM164's mechanistic links to ferroptosis and autophagy.

Main Results:

  • TMEM164 expression is significantly downregulated in LUAD, correlating with poor prognosis.
  • Upregulating TMEM164 inhibits LUAD cell proliferation, migration, and invasion.
  • TMEM164 enhances ferroptosis via ATG5-dependent autophagy and shows synergistic effects with anti-PD-1 therapy in vivo.

Conclusions:

  • TMEM164 plays a critical role in suppressing LUAD progression.
  • Modulating TMEM164 offers a promising therapeutic strategy for lung adenocarcinoma.
  • TMEM164 enhances ferroptosis and anti-tumor immunity, suggesting its potential in combination therapies.

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